Davidson J M
Department of Pathology, Vanderbilt University, School of Medicine, Research Service, Nashville, TN 37232-2561.
Eur Respir J. 1990 Oct;3(9):1048-63.
The lung contains a host of extracellular matrix components that comprise the supporting and adhesive elements of conducting airways, alveoli and the vascular tree. While none of these components is unique to the lung, their peculiar distribution determines the architecture and function of this gas exchange organ. Cells and tissues of the lung interact with the matrix through a variety of surface receptors, especially the integrins and adhesive molecules, some of which may play important roles in lung injury and repair. Collagen type I is the predominant determinant of tensile strength, but as many as 11 other genetic types of collagen with specialized adhesive and connecting functions can be found in various lung structures, including cartilage and basement membranes. Excessive matrix accumulation in the lung is the result of a complex set of influences on gene regulation, part of which may be due to the presence of inflammatory cytokines that directly stimulate matrix synthesis. However, degradation and turnover of the matrix are also critical processes influenced by many of the same mediators. Collagenase and gelatinase (type IV collagenase) are tightly-regulated metalloenzymes that, together with a set of specific inhibitors of metalloproteinases, determine the net abundance and distribution of collagen. Elastases of several biochemical types are also under tight regulation by proteinase inhibitors. Elastin is essential to lung function at the level of alveolar wall resiliency and patency, and loss of elastin in emphysema appears to be due to uncontrolled degradation of the embryologically-established pattern of elastic fibres accompanied by nonfunctional replacement as a response to injury. Injury to the vascular endothelium of the lung, as well as other physiological insults that elevate pulmonary blood pressure, can lead to the excessive accumulation of collagen and elastin in the conductance and resistance arteries of the pulmonary circulation. Mechanical stress and endothelial injury may mediate the medial hypertrophy of these vessels. Extracellular matrix components are critically involved in every stage of lung biology: development, normal function and acute and chronic disease states. To date, only glucocorticoids, cross-linking inhibitors, and protease inhibitors have been used in a general attempt to suppress either excessive matrix accumulation or loss. More detailed understanding of the regulation and specific interactions of matrix components is central to the analysis of disease states and the development of appropriate therapeutic strategies.
肺包含大量细胞外基质成分，这些成分构成了传导气道、肺泡和血管树的支撑和黏附元件。虽然这些成分没有一种是肺所特有的，但它们独特的分布决定了这个气体交换器官的结构和功能。肺的细胞和组织通过多种表面受体与基质相互作用，尤其是整合素和黏附分子，其中一些可能在肺损伤和修复中起重要作用。I型胶原蛋白是抗张强度的主要决定因素，但在包括软骨和基底膜在内的各种肺结构中，还能发现多达11种其他具有特殊黏附及连接功能的基因类型的胶原蛋白。肺中基质的过度积累是一系列复杂的基因调控影响的结果，部分原因可能是存在直接刺激基质合成的炎性细胞因子。然而，基质的降解和周转也是受许多相同介质影响的关键过程。胶原酶和明胶酶（IV型胶原酶）是受严格调控的金属酶，它们与一组金属蛋白酶特异性抑制剂共同决定了胶原蛋白的净丰度和分布。几种生化类型的弹性蛋白酶也受到蛋白酶抑制剂的严格调控。弹性蛋白对于肺泡壁弹性和通畅性水平的肺功能至关重要，肺气肿中弹性蛋白的丧失似乎是由于胚胎期建立的弹性纤维模式不受控制地降解，并伴有作为损伤反应的无功能替代。肺血管内皮的损伤以及其他升高肺动脉压的生理损伤，可导致肺循环中传导和阻力动脉中胶原蛋白和弹性蛋白的过度积累。机械应力和内皮损伤可能介导这些血管的中层肥厚。细胞外基质成分在肺生物学的每个阶段都至关重要：发育、正常功能以及急性和慢性疾病状态。迄今为止，一般仅使用糖皮质激素、交联抑制剂和蛋白酶抑制剂来抑制基质的过度积累或丧失。对基质成分的调控和特定相互作用的更详细了解对于疾病状态分析和适当治疗策略的制定至关重要。
